PGE₂ Involved In NLRP3-Mediated Skin Wound Healing And The Myofibroblast/Macrophages Interaction In Mice

The healing of skin wounds is a complex process,which requires the cooperation of various cells and the participation of various cytokines.Among them,the interaction of macrophages and myofibroblasts is indispensable for tissue repair.The pattern recognition receptor NOD-like receptor protein 3（NLRP3）in the innate immune system may have a regulatory role in the tissue repair process.Prostaglandin E₂（PGE₂）is an important biologically active substance produced after the activation of NLRP3.However,the regulatory mechanism of NLRP3 and PGE₂ on the interaction between macrophages and myofibroblasts is still unclear.In this study,NLRP3^-/-mice and wild-type C57BL/6J mice were used as experimental animal models to explore the roles of NLRP3 and PGE₂ in the process of skin wound healing in mice.This study confirmed that the process of skin wound healing was impaired in NLRP3^-/-mice compared to that in wild-type C57BL/6J mice,by constructing a mouse skin injury model.It was confirmed that NLRP3 and PGE₂ play roles in mediating the interaction between myofibroblasts and macrophages,by constructing a mouse myofibroblast-macrophage interaction model.Among them,wild-type C57BL/6J mouse myofibroblast conditioned medium（MFb CM）was able to enhance arginase activity,chitinase 3 activity in alternatively activated macrophages（AAMs）Chitinase-3-like Protein1（Ym1）expression and anti-inflammatory factor IL-10 secretion,while decrease the production of pro-inflammatory factor nitric oxide（NO）.MFb CM in NLRP3^-/-mice had no effect on arginase activity and IL-10 secretion in AAMs,but inhibited NO production.Moreover,this study confirmed that PGE₂ concentration was noticed lower in NLRP3^-/-MFb CM than that in C57BL/6J MFb CM,suggesting that NLRP3 and PGE₂ are closely related to the process of mediating skin wound healing.The study further confirmed that co-treatment of AAMs with exogenous PGE₂ and NLRP3^-/-MFb CM could induce arginase activity,IL-10 secretion and NO production in AMMs.All these results indicated that NLRP3 involved in the healing process of mouse skin wounds,and NLRP3 may regulate the interaction between myofibroblasts and AAMs by affecting the secretion of PGE₂,thereby participating in the healing process of mouse skin wounds.